BLOOD AND BLOOD RELATED HAEMOSTASIS (part-2).pptx

BLOOD AND BLOOD RELATED DISORDERS

1. HAEMOSTASIS (part-2)

2. CONTENTS Bleeding disorder classification vascular disorder inherited vascular disorder acquired vascular disorder platelet disorder thrombocytopenia

3. HAEMORRHAGIC (bleeding) DISORDER Characterised by defective haemostasis with abnormal bleeding. May be spontaneous in the form of small haemorrhages into the skin and mucous membranes. OR May be excessive external or internal bleeding following trivial trauma and surgical procedure.

4. classification CAUSES ARE BROADLY DIVIDED INTO FOLLOWING GROUPS: VASCULAR ABNORMALITIES PLATELET ABNORMALITIES DISORDER OF COAGULATION FACTOR FIBRINOLYTIC DEFECTS

5. VASCULAR DISORDER A.K.A NON-THROMBOCYTOPENIC PURPURAS OR VASCULAR PURPURAS COMMONLY CALLED AS SUCH AS THE CAUSE LIES IN THE VASCULAR WALL- DAMAGED ENDOTHELIUM, ABNORMALITY IN SUBENDOTHELIAL MATRIX, ABNORMAL FORMATION OF BLOOD VESSELS. DIVIDED INTO 2 TYPES INHERITED VASCULAR BLEEDING DISORDER ACQUIRED VASCULAR BLEEDING DISORDER

6. HEREDITARY HAEMORRHAGIC TELANGIECTASIA Uncommon Autosomal dominant disorder Begins in childhood Abnormal telangiectatic ( dialated ) capillaries causes malformation in skin & mucosal surface. Lips Tongue Nose Eye Palms Soles INHERITED VASCULAR BLEEDING DISORDER

7. Inherited disorder of connective tissue matrix Marfan’s syndrome Ehlers-Danlos syndrome Pseudoxanthoma elasticum Fragile skin vessel and easy bruising INHERITED VASCULAR BLEEDING DISORDER

8. ACQUIRED VASCULAR BLEEDING DISORDER HENOCH-SCHONLEIN PURPURA: A.k.a anaphylactoid purpura Self limiting type of hypersensitivity vasculitis in children and young adults Produces purpuric rash on extensor surface i.e arms, legs, buttocks Abdominal pain due to bleeding into the GIT DESPITE THE FEATURE COAGULATION TEST ARE NORMAL immune complexes are deposited in the vessel wall consisting of IgA, C3 & fibrin

9. ACQUIRED VASCULAR BLEEDING DISORDER HAEMOLYTIC-URAEMIC SYNDROME: Disease of infancy and early childhood in which there is bleeding tendancy and varying degree of acute renal failure. Remains confined to kidney where hyaline thrombi are seen in the glomerular capillaries.

10. ACQUIRED VASCULAR BLEEDING DISORDER SIMPLE EASY BRUISING (Devil’s pinches) Easy bruising Unknown cause Common phenomenon in women of child bearing age group

11. ACQUIRED VASCULAR BLEEDING DISORDER INFECTION Many infection causes vascular haemorrhages either by causing toxic damage to the endothelium or DIC (disseminated intravascular coagulation) Prone to occur in septicaemia and severe measles.

12. ACQUIRED VASCULAR BLEEDING DISORDER Drug reaction: Certain drugs form antibodies and produce hypersensitivity (or leukocytoclastic) vasculitis responsible for abnormal bleeding.

13. ACQUIRED VASCULAR BLEEDING DISORDER Steroid purpura: Long term steroid therapy or cushing’s syndrome may be associated with vascular purpura due to defective vascular support.

14. ACQUIRED VASCULAR BLEEDING DISORDER Senile purpura: Atrophy of the supportive tissue of cutaneous blood vessels in old age may cause senile atrophy, especially in the dorsum of forearm and hand.

15. ACQUIRED VASCULAR BLEEDING DISORDER Scurvy: Deficiency of vitamin K Defective collagen synthesis cause skin bleeding, bleeding into muscle and occasionally into GI tract.

16. PLATELET DISORDER Platelet produce bleeding disorder by one of the following 3 mechanism: Reduction in number of platelets Rise in platelet count Defective platelet function

17. THROMBOCYTOPENIA Reduction in peripheral blood platelet count below lower limit of normal (150,000 per microliter) of blood. Associated with abnormal bleeding includes Sponatneous skin purpura Mucosal haemorrhages Prolonged bleeding after trauma

18. IMPAIRED PLATELET PRODUCTION DILUTIONAL LOSS ACCELERATED PLATELET DESTRUCTION SPLENIC SEQUESTRATION THROMBOCYTOPENIA

19. DRUG INDUCED THROMBOCYTOPENIA Drugs depress the megakaryocyte production Chemotherapeutic agents antibiotics Drugs used in cardiovascular diseases diclofenac acyclovir heparin Excessive consumption of ethenol

20. Clinically patient presents with acute purpura Platelet count is low often below 10000 per microlitere Shows normal or increased number of megakaryocyte IMMEDIATE TREATMENT Stop or replace suspected drug Temporary support with plasmapheresis or glucocorticoids.

21. HEPARIN INDUCED THROMBOCYTOPENIA Usually not severe Platelet count does not fall below 20,000 per microlitere Patient is more prone to develop thrombosis MECHANISM: formation of antibody against PF-4 It activates the endothelial cells and initiates thrombus formation Happens in very few cases, after patient has received heparin for 5-10 days

22. Immune thrombocytopenic purpura Immunological destruction of platelets Normal or increased number of megakaryocyte in bone marrow On basis of duration is classified into 2 type: acute & chronic

23. ACUTE ITP Self limiting Usually in children recovering from viral illness or upper respiratory illness Onset is sudden and severe but recovery is within few weeks to 6 months. MECHANISM : formation of immune complex which contain viral antigen, by formation of antibody for viral antigen it cross reacts with platelet leading to immunological destruction CHRONIC ITP Common in adults Mostly women of child bearing age (20-40 years) persists for several years Similar thrombocytopenia may be associated with AIDS and autoimmune thyroiditis Pathogenesis is explained by formation of anti-platelet autoantibody by IgG antibody synthesized in spleen

24. Usual manifestation: Petechial haemorrhages , easy bruising and mucosal bleeding Menorrhagia in women Nasal bleeding Bleeding from gums Intracranial haemorrhage RARE Splenomegaly & Hepatomegaly = chronic ITP CLINICAL FEATURE

25. TREATMENT Spontaneous recovery in 90% (acute ITP) 10% (chronic ITP) Main focus is on reducing the level and source of autoantibodies Usually possible by corticosteroid therapy, immunosuppressive drugs ( e.g vincristine, cyclophosphamide and azathioprine) Splenectomy (chronic ITP) removal of major site of platelet destruction, major source of auto antibody synthesis. Platelet transfusion in patient with severe haemorrhage

26. THROMBOTIC THROMBOCYTOPENIC PURPURA Thrombotic microangiopathies Characterised by triad of: thrombocytopenia Microangiopathic haemolytic anemia Formation of hyaline fibrin microthrombi Often lethal in young adults Intravescular microthrombi composed of platelet and fibrin

27. PATHOGENESIS Initiated by endothelial injury followed by release of von Willebrand factor and other procoagulant material from endothelial cells leading to formation of microthrombi. Trigger comes from immunologic damage by diverse condition i.e. pregnancy Metastatic cancer High dose chemotherapy HIV infection

28. CLINICAL FEATURE Fever Transient neurologic deficits Renal failure Spleen may be palpable

29. LAB FINDINGS Thrombocytopenia Microangiopathic haemolytic anemia Leucocytosis Normal or slightly increased megakaryoctes

30. To be continued….